Actively Recruiting
A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
Led by Krystal Biotech, Inc. · Updated on 2025-07-22
15
Participants Needed
3
Research Sites
145 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to evaluate safety and pharmacodynamics of KB408 in adults with AATD with a PI\*ZZ or PI\*ZNull genotype. Three planned dose levels of KB408 will be evaluated in single dose escalation cohorts. Repeat dosing will be evaluated at the mid dose level. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. In the repeat dose and the high dose cohorts, subjects must wash out from IV AAT for at least 10 days, as applicable.
CONDITIONS
Official Title
A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
Who Can Participate
Eligibility Criteria
You may qualify if you...
- The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and be willing and able to comply with study procedures and instructions.
- Subject is aged 18 to 70 years at the time of informed consent.
- Subject has a genetically confirmed diagnosis of AATD with a PIZZ or PIZNull genotype.
- For Cohort 2b and Cohort 3: Subjects receiving AAT augmentation therapy must be willing to washout for at least 10 days prior to Screening and remain off augmentation therapy for the study duration.
- For Cohort 2b and Cohort 3: Serum AAT level less than 11 µM at Screening.
- Willing to remain on a stable regimen of treatment during the study.
- Resting oxygen saturation 92% or higher on room air at Screening.
- Clinically stable and in good general health except for AATD, as determined by the Investigator.
You will not qualify if you...
- Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after bronchodilator is less than 40% at Screening.
- Diffusing capacity of the lungs for carbon monoxide (DLCO) less than 30 percent predicted within 2 years prior to or at Screening.
- Known ongoing or history of clinically significant pulmonary impairment other than AATD.
- Pulmonary exacerbation within 6 weeks (42 days) prior to first dose.
- Initiation of any new chronic therapy or change in ongoing routine therapy within 28 days of first dose.
- Participation in another interventional clinical study or investigational treatment within 30 days or 5 half-lives of first dose.
- History of or listed for solid organ transplantation or major lung surgery within 6 months of first dose.
- Any clinical condition or illness that may impact ability to complete study or increase safety risk, including substance abuse.
- Active oral herpes infection within 30 days prior to first dose.
- Significant hepatic dysfunction including AST or ALT ≥3 times upper limit of normal, total bilirubin ≥2 times upper limit of normal (unless Gilbert's syndrome), or liver cirrhosis with portal hypertension symptoms.
- History of cigarette smoking, tobacco use, e-cigarettes, or recreational inhalants within 6 months of Screening.
- Unwillingness to refrain from smoking, e-cigarette use, or vaping during the study.
- Positive urine cotinine result consistent with active smoking at Screening (except if due to nicotine replacement therapy).
- Abnormal hematology or chemistry tests at Screening as defined (platelets <100 x10^9/L, hemoglobin <9 g/dL, white blood cell count <3 or >15 x10^9/L, sodium <130 or >150 mmol/L, potassium <3 or >5.5 mmol/L, carbon dioxide <16 mmol/L, creatinine >2 mg/dL).
- Known noncompliance or unlikely to comply with study protocol.
- Females who are pregnant or nursing.
- Unwilling to comply with contraception requirements per protocol.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 3 locations
1
University of Florida, Gainesville
Gainesville, Florida, United States, 32610
Actively Recruiting
2
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Actively Recruiting
3
Renovatio Clinical
The Woodlands, Texas, United States, 77380
Actively Recruiting
Research Team
D
David Sweet, MD, PhD
CONTACT
B
Brittani Agostini, RN, CCRC
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
4
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